Therefore hypertension usually precedes the onset of microalbumin

Therefore hypertension usually precedes the onset of microalbuminuria.3 BP control modulates Gefitinib mw the progression not only of microangiopathy (diabetic kidney disease and retinopathy) but also of macroangiopathy (Coronary heart disease (CHD) and

stroke). In microalbuminuric people with type 2 diabetes, observational studies have shown an association between poor glycaemic control and progression of albuminuria. A number of studies have identified a strong independent association between hyperglycaemia and the rate of development of microvascular complications.4 The large observational WESDR study5 indicated an exponential relationship between worsening glycaemic control and the incidence of nephropathy as well as retinopathy and neuropathy. The UKPDS has clearly shown the importance of targeting glycosylated haemoglobin (HbA1c) levels close to normal (HbA1c < 7.0%) in people with type 2 diabetes. A modest decrease in HbA1c over 10 years from 7.9 to 7.0% lowered the risk of microvascular endpoints

with the onset of microalbuminuria being reduced by 25%.6 These findings are supported by a study of intensified glycaemic control in non-obese Japanese check details subjects with type 2 diabetes.7 In the UKPDS, there was no significant reduction in the risk of progression from microalbuminuria to proteinuria with intensive blood glucose control.8 The AusDiab study collected information on albuminuria, measured as a spot albumin: creatinine ratio (ACR) (mg/mmol) with microalbuminuria being between 3.4 and 34 mg/mmol and macroalbuminuria at >34 mg/mol.9 The prevalence of albuminuria increased with increasing glycaemia. People with diabetes and impaired glucose tolerance had an increased risk for albuminuria compared with those with normal glucose tolerance, independent of other known risk factors for albuminuria (including age and sex). Hyperglycaemia is an important determinant of the progression of normoalbuminuria to microalbuminuria in diabetes.

DNA Damage inhibitor Strict blood glucose control has been shown to delay the progression from normoalbuminuria to microalbuminuria or overt kidney disease6 and from normo- or microalbuminuria to overt kidney disease.7 The influence of intensive glycaemic control is greatest in the early stages of CKD although some observational studies suggest an association of glycaemic control with the rate of progression of overt kidney disease and even end-stage kidney disease (ESKD).10 The American Heart Association (AHA) has undertaken a review of the DCCT, UKPDS, ACCORD, ADVANCE and VA Diabetes trials and on the basis of the review issued a Scientific Statement addressing intensive glycaemic control in relation to cardiovascular events.11 While the AHA review is focused on cardiovascular events, the statement is relevant to the consideration of the management of CKD given the strong association between CKD and CVD in people with type 2 diabetes.

Interleukin-15 (IL-15) produced by hyperplasic stroma and epithel

Interleukin-15 (IL-15) produced by hyperplasic stroma and epithelial cells [22] selleck could attract T cells and support their expression of P. Augmented IL-15 production by prostate cells could

be a contributory factor facilitating the transendothelial migration of CD56+ NK cells to the stroma of BPH tissue and support their P expression [16]. In our study, flow cytometry analysis revealed negligible expression of P in T lymphocytes and NKT and NK cells in the PCa tissue; this may be attributable to tumour activity leading to the development of a chemical barrier around the tumour that probably inhibits TIL infiltration and activation [23, 24]. The increased production of reactive nitrogen species by the tumour actively models the tumour environment, leading to an altered chemokine profile and changes in capacity to recruit T lymphocytes [25]. In contrast to proinflammatory dominance in patients with BPH, increased levels of IL-4 have been observed in patients with androgen-independent PCa [26]. Furthermore,

IL-4 was shown to enhance the expression of the PSA gene, whose protein product is a prostate-specific glycoprotein overexpressed in patients with PCa [27]. PSA, because of its glycoprotein structure, could GSI-IX mw support the local anti-inflammatory response and induce alternative activation of antigen-presenting cells, leading to inefficient activation of cell-mediated immunity [28]. In such cases, tumour cells could deeply invade surrounding tissues and enter systemic circulation. Negligible CD3+ T cell infiltration as well as reduced NK cell infiltrate with low P content was found in Dapagliflozin PCa tissue and this could be responsible for the inefficient control of tumour invasion. Moreover, a negative correlation between PSA values and overall

percentage of P+ cells and P-expressing T and NK cells in the prostate tissue was observed only in PCa patients, suggesting that the low percentage of P+ cells in the prostate tissue could be responsible for an increased risk of tumour development and progression. In conclusion, our findings showed that the low frequency of P+ lymphocytes, including T, NKT and NK cells, in prostate tissue of patients with BPH and, particularly, PCa could be the consequence of local tissue microenvironment and one of the mechanisms involved in the pathogenesis of prostate hyperplasia following malignant alteration. This investigation was supported by the grants from the Croatian Ministry of Science, Education and Sports (projects no. 062-0620096-0094 and 062-0000000-0220). The authors thank Ksenija Tulic for assistance in laboratory work. The authors declare that they have no conflict of interest. “
“Interleukin-15 (IL-15) is an inflammatory cytokine whose role in autoimmune diseases has not been fully elucidated. Th17 cells have been shown to play critical roles in experimental autoimmune encephalomyelitis (EAE) models.

VIP/VPAC1 expression did not vary in BALB/c glands with mouse age

VIP/VPAC1 expression did not vary in BALB/c glands with mouse age and, in contrast with NOD glands, freshly isolated acinar cells seemed not to be prone to apoptosis. Acinar cells from NOD mice could be further induced to Enzalutamide apoptosis with a concentration

of TNF-α (10 ng/ml) that was almost ineffective in normal acinar cells. VIP inhibited TNF-α-induced apoptosis in NOD acinar cells through a VPAC1/cAMP/PKA pathway, while neither VPAC2 receptors nor the neuropeptide could be detected in acini, indicating that their expression in whole glands would not correspond to acinar cells. Finally, we found a reduced phagocytic index of NOD macrophages to engulf apoptotic acinar cells compared to normal macrophages, but their basal inflammatory phenotype was suppressed during phagocytosis and VIP stabilized this suppressor regulatory phenotype. It is noteworthy that the time–course of VIP/VPAC1 relative expression decline is similar to the kinetics of nNOS activity loss shown previously and parallels NVP-LDE225 ic50 the reduction in the secretory response to muscarinic acetylcholine receptor stimulation [12]. It also coincided with the loss of acinar cell homogeneous structure of the glands and a higher ductal to acinar cell ratio in the glands at 16 weeks of age [12]. The localization of this enzyme is normally confined

to neural fibres in close proximity to gland epithelial cells where NO contributes to salivary flow. Consistent with this, NOD mice submandibular glands showed a

reduced NOS activation through VIP receptors that coincided with the reduction in salivary flow [15]. While VIP can induce NOS in peripheral and central neurones, VIP expression is regulated by neural NOS activity and knock-out mice for neural NOS isoform express lower neuronal VIP levels [29]. In rat salivary glands VIP is localized in nerve fibres rather than in acinar cells, being mainly released from nerves surrounding acini where it displays trophic effects on epithelial cells [17,18]. In fact, the release of trophic and anti-apoptotic stimuli from nerve terminals with long-term effects on salivary gland parenchyma is the rationale of a newly designed device to restore salivary flow in patients with SS and other sicca-associated pathologies [30]. Acinar cells from both normal and NOD isometheptene submandibular glands express only VPAC1 receptors, as reported previously [16]. In these cells, VIP was able to reduce apoptosis via cAMP/PKA pathway, as derived from the fact that H89 reversed VIP effect on bax expression [16] and Bad phosphorylation, a step previous to the loss of its apoptotic effect through binding to 14–3–3 in cytosol [31]. Evidence shown here indicates that acinar epithelium of NOD but not BALB/c glands present increased apoptosis along with a dysregulated NF-κB basal activation consistent with a predominant apoptosis-to-survival intracellular set-point.

19–22 Infection with Listeria monocytogenes in mice is a widely u

19–22 Infection with Listeria monocytogenes in mice is a widely used experimental model for identifying the immune mediators of innate and adaptive host defence against intracellular bacterial pathogens.23–25 Interferon-γ produced by NK and both CD4+ and CD8+ T-cell subsets each play important roles in innate host defence at early time-points after this infection.26–29 At later infection time-points, the

Selumetinib mw expansion of L. monocytogenes-specific CD8+ and CD4+ T cells coincides with bacterial eradication, and thereafter the absolute numbers of pathogen-specific cells contract, and are maintained at ∼ 5 to 10% of peak expansion levels.24,25 During secondary infection, L. monocytogenes-specific T cells re-expand and rapidly confer sterilizing immunity to infection. Although the cellular mediators that confer protection in each phase of L. monocytogenes infection have been

identified, the specific cytokine signals that activate and sustain these cells remain largely undefined. Given the potency whereby IL-21 stimulates the activation of NK, NVP-BGJ398 CD8+ and CD4+ T cells, and the importance of these cells in host defence against L. monocytogenes, the requirement for IL-21 in innate and adaptive immunity after this acute bacterial infection was examined in this study. Interleukin-21-deficient mice on a C57BL/6 (B6) background were obtained from Dr Matthew Mescher through Lexicon Genetics and the Mutant Mouse Regional Resource Centers. B6 control mice were purchased from the National Cancer Institute (Bethesda, MD). Mice with individual defects in IL-12P40 or type I IFN receptor, and mice with combined defects in both IL-12P40 and type I IFN receptor (i.e. double

knockout; DKO) have been described.30,31 Mice with combined defects in IL-21, IL-12, and type I IFN receptor (triple knockout; TKO) were generated by inter-crossing IL-21-deficient mice with type I IFN receptor-deficient mice, and then inter-crossing these mice with DKO mice. All experiments were performed under University of Minnesota Institutional Animal Care and Use Committee approved protocols. The wild-type L. monocytogenes strain 10403s, recombinant Dimethyl sulfoxide L. monocytogenes ovalbumin (Lm-OVA), and recombinant Lm-OVA ΔactA that allow a more precise analysis of the immune response to the surrogate L. monocytogenes-specific H-2Kb OVA257–264 antigen have each been described.30–32 For infections, L. monocytogenes was grown to early log phase (optical density at 600 nm 0·1) in brain–heart infusion medium at 37°, washed, and diluted with saline to 200 μl final volume and injected intravenously. At the indicated time-points after infection, the number of recoverable L. monocytogenes colony-forming units (CFUs) in the organs of infected mice were quantified by homogenization in saline containing Triton-X (0·05%), and plating serial dilutions of the homogenate on agar plates as described.

e , different levels of hygiene might allow different types of ba

e., different levels of hygiene might allow different types of bacterial species to populate), which has been shown to correlate with HIV seroprevalence.16 O’Farrell et al. used clinician’s assessments Carfilzomib nmr of ‘wetness’ around the glans or coronal sulcus to show that uncircumcised men had significantly higher rates of wetness when compared to circumcised men. Importantly, they also found a 66.3% HIV seroprevalence in men with any level of penile wetness

when compared to 45.9% in those with no wetness (P < 0.001). These results together suggest that the presence of the foreskin can substantially influence the microenvironment on or near the surface of the penis and that this may in turn affect HIV susceptibility.

Prior to the widely publicized clinical benefit of male circumcision, Hussain et al.17 published a report analyzing immune cells in the genital tract. They found no difference in the number of Langerhans (LCs) or CD4+ T cells between the inner and outer foreskin of adult men. Later reports have found conflicting results (Table I): one found more HIV-susceptible cells in the outer when compared to either inner foreskin or glans tissue, and another reported more cells in the inner than the outer foreskin.4,18 A study published by our own group, in collaboration with Dr. Robin Shattock’s group, showed that initial differences in LCs and CD4+ T-cell (glans >> inner > outer) densities were not seen after the tissues were allowed to culture for a few days.4,5,18 Therefore, it is possible that some of the previously observed differences were a result of surgically induced trauma to the tissues and may not accurately reflect normal tissues. To further understand the dynamics

of the immunologic environment in the male genital tract, Fahrbach et al. 19 examined target cell activity in the inner and outer foreskin in response to inflammatory cytokines. Using long-term tissue explant cultures and fluorescent microscopy, they showed that LCs and CD4+ T cells in the inner foreskin were significantly Liothyronine Sodium more responsive to certain cytokines than those in the outer foreskin. One possible explanation for these findings is that the inner foreskin is more permeable to external agents and stimuli than the outer foreskin. This increased permeability may then relate to increased viral susceptibility in the inner foreskin when compared to other penile surfaces. An appealing early theory proposed that the inner foreskin’s keratin, or cornified, layer was thinner than that of other penile surfaces. A thinner keratin layer potentially allows HIV to reach resident target cells more easily and hence makes uncircumcised men more susceptible to infection. To support this, a study using penile tissue from cadaveric donors reported that the keratin of the inner foreskin was approximately 1.5 subjective units thinner than that of the outer foreskin or glans penis.

(FV1:1), hepato- & splenomegalia Colectomized Also suffered from

(FV1:1), hepato- & splenomegalia Colectomized Also suffered from Neurofibromatosis Recklinghausen Gingival hypertrophia Acne Colectomi and ileostomia due to pancolitis; Bone marrow transplantation may 2010 Colectomized years ago Chronic pulmonary aspergillosis, died from respiratory insufficiency December 2011 Died February 2008 1994 diagnosed as Crohn’s disease, colectomized, Selleck Carfilzomib recurrent severe pulmonary infections incl B. cepasia, Severe pulmonary insufficiency. Home oxygen treatment. CGD diagnosed post mortem Severe acne Proctocolitis with

fistulae. Colostomized Severe parodontitis. Total tooth extraction done deletion splice site del 75_76 GTc c.682+1G>A p.Tyr26HisfsX26 Del exon 7 p.Trp193_Gly228del [16] Novel Diagnosed in 2012 Recurrent mucocutaneus abscesses, chronic gingivitis but no pulmonary symptoms An overview of the clinical status for all patients is presented in Table 1. The clinical history of six of the patients has previously been described in detail[19-22]. Genomic DNA was isolated from whole blood collected in EDTA with the Wizard Genomic DNA isolation kit from Promega (Nacka, Sweden). Custom synthesized primers were ordered from Invitrogen (Taastrup, Denmark). The 5′-fluorescently labelled oligonucleotides

were ordered from Applied Biosystems (Stockholm, Sweden). The Gene Scan selleck chemical analysis was performed as previously described [20, 23]. The ratio of functional genes to pseudogenes was determined by calculating the peak areas corresponding to the two fragments differing by only 2 bp. The five genes encoding the components of the NADPH oxidase complex were analysed in a sequential pattern with amplification and sequencing methods previously described [20, 24]. The molecular background of the Danish patients diagnosed with CGD and followed in the clinic was investigated, this cohort includes 27 patients. Sixteen of 27 patients (59%) had autosomal recessive mutations located in Org 27569 either NCF1 or CYBA. No mutations were observed in NCF2 or NCF4. Eleven patients had an X-linked mutation of the CYBB gene (Table 1). The present ages of the patients range from 14 to 60 years. Three

different mutations were found in a group of six patients. Patients 3, 4, 5 and 6 are related and harbour the same missense mutation p.Ala124Val in exon 6 of CYBA. Patients 1 and 2 are unrelated and both have a mutation in the 5′ splice site in intron 4, leading to the deletion of exon 4 in the mRNA transcript (Fig. 1). The deletion of exon 4 does not change the reading frame. At present, both patients are without symptoms even though their DHR test is negative. Patient 2 is only heterozygous for the splice site mutation but harbours a deletion of exon 6 on the other allele. In accordance with this finding, carrier status for the splice site mutation was only detected in the mother (Fig. 1). Ten different mutations were detected in the 11 patients with X-linked CGD. Patients 8 and 9 are brothers and have the same missense mutation p.Pro56Leu.

Recent studies have identified a variety of NLRP3 inflammasome ac

Recent studies have identified a variety of NLRP3 inflammasome activators

including whole live bacteria, fungal and viral pathogens, as well as various AZD9668 price microbial-associated molecular patterns and DAMPs [2]. In addition, cellular stress triggered by factors ranging from oxidative stress to lysosomal damage appears sufficient to activate NLRP3 [3]. The mechanisms by which these molecules of diverse origins and structures can each trigger the NLRP3 inflammasome remain unclear. However, the generation of ROS seems to be a unifying factor, consistently mediating NLRP3 activation across several stimuli [4]. Recently, Zhou and colleagues demonstrated that mitochondrial (mt) ROS are critical for NLRP3 inflammasome activation [5]. Accumulation of ROS-producing mitochondria either by repressing mitochondrial autophagy or by pharmacological inhibition of the mitochondrial electron transport chain resulted in increased release of

IL-1β and IL-18 in response to LPS and ATP, or exposure to monosodium urate (MSU) crystals [5, 6]. The role played by NLRP3 in mediating release of IL-1β is well established, but it remains unclear whether the NLRP3 inflammasome might also have cytokine-independent impacts on host cell responses by acting through alternative pathways. We therefore employed MSU crystals, which elicit robust ROS production and consequently oxidative stress, but not IL-1β release, to examine the role of NLRP3 in non-inflammatory pathways. Here, we show that the NLRP3 Regorafenib datasheet inflammasome controls cellular responses

to DNA damage after genotoxic stress driven by MSU crystals or γ-radiation. Dendritic cells (DCs) from Nlrp3−/− and casp-1−/− mice exhibited reduced levels of DNA fragmentation as a result of enhanced DNA repair activity mediated by upregulation of double-strand and base-excision DNA repair genes. Moreover, DNA damage triggered the activation of the pro-apoptotic p53 pathway in WT DCs, but less so in Nlrp3−/− and casp-1−/− cells. These findings demonstrate that the NLRP3 inflammasome plays 3-mercaptopyruvate sulfurtransferase an important role in DNA damage responses (DDR) to oxidative and genotoxic stress, supporting cell death, and ultimately cell death associated inflammation. To identify new cytokine-independent pathways regulated by NLRP3 during oxidative stress, we used MSU crystals, which activate the NLRP3 inflammasome through production of ROS but in the absence of a priming signal do not induce IL-1β and IL-18 production [7, 8]. Cellular transcriptomes of MSU-treated DCs were generated using high-density mouse oligonucleotide Affymetrix gene arrays. Differentially expressed genes (DEGs) were identified in MSU-stimulated DCs from WT and Nlrp3−/− mice compared with their respective untreated controls.

These findings led to experiments designed to assess infection of

These findings led to experiments designed to assess infection of human skin in a controlled study of live spirochetes infecting full thickness human skin explants (keratomes). Blinded analysis of low power fields Selleckchem Gefitinib assessed the number of CD1 expressing cells within the dermis and epidermis. There were no significant changes in the number, apparent brightness or size of CD1a expressing Langerhans cells (LCs) in the epidermis, when comparing infected or sham-treated

keratomes (Fig. 1B and C). The number of CD1a expressing cells in the dermis (4.1% of all cells) increased slightly after infection (6.1%) but did not reach statistical significance (p=0.34). However, the number of CD1b (p<0.0027) or CD1c (p<0.0086) expressing cells showed a significant increase after infection (Fig. 1C). Also, we observed marked increases in brightness of staining in each of three experiments. Although SB203580 CD1d could be detected at very low levels in flow cytometry experiments

(Fig. 2), CD1d staining was not seen at levels higher that isotype-matched staining control samples (Fig. 1C). We conclude that evaluation of CD1a induction was limited by constitutively positive LCs, but increased CD1b and CD1c expression is induced during B. burgdorferi infection of human skin. To study the cellular mechanisms of CD1 induction by B. burgdorferi, we measured CD1 expression on human monocytes in culture. To determine whether the events seen ex vivo could be modeled in vitro, we first measured CD1 expression on monocytes after infection with live bacteria or by treatment of cells with lipids extracted from bacteria with chloroform and methanol. Fresh monocytes and control monocytes sham treated with medium for 3 days did not detectably express CD1a, CD1b or CD1c proteins at the surface, but CD1d was detected at low density on some cells (Fig. 2A and data not shown). Ex vivo infection with live spirochetes (data not shown) or cell wall lipids (Fig. 2A) increased cell surface expression of CD1a, CD1b and CD1c proteins to high levels. CD1a surface density increased

in a dose-dependent fashion (Fig. 2B). The resultant CD1a cell surface expression Phosphatidylinositol diacylglycerol-lyase was sufficient to activate a CD1a autoreactive T-cell line (Fig. 2C). The low levels of baseline expression of CD1d were unaltered or slightly decreased, so that they were undetectable (Fig. 2A). These results confirm that B. burgdorferi potently activates group 1 CD1 expression on monocyte-derived DCs in a model that mimics many aspects of the in vivo observations. In particular, these data show selective upregulation of group 1 CD1 proteins over 3 days. Activation of myeloid cells by B. burgdorferi lipoproteins is mediated through TLR-2 29. Also, a synthetic TLR-2 agonist triacyl-CSK4, which mimics the structure of the N-terminus of a borrelial lipoprotein, can induce CD1 expression 30.

Recent studies have shown that separate, exogenous activation of

Recent studies have shown that separate, exogenous activation of inflammasome pathways is not always stringently required for IL-1β cleavage, especially in monocytes or in situations in which strong cellular activation leads to ATP release and autoinduction of the inflammasome 45–47. Western blotting showed that monocytes treated with ATP alone did not produce detectable cleaved IL-1β, but triacyl-CSK4 with or without added ATP produced detectable

cleaved IL-1β (Fig. 4D). CD1 induction correlated with IL-1β cleavage, as flow cytometric measurement of surface CD1a induction showed that triacyl-CSK4, but not ATP was sufficient to induce CD1 (Fig. 4D). Thus, AP24534 TLR-2 activation is necessary and sufficient, and so it can be considered

the main driver of CD1 induction under these conditions. AZD5363 supplier Separate, pharmacologic activation by ATP contributes quantitatively to the response. A now widely used nomenclature system was originally developed in which the five human CD1 APCs were divided into two groups based on amino acid sequence homology 48. New data, including the responses to B. burdorferi reported here, show that group 1 protein (CD1a, CD1b, CD1c) and group 2 (CD1d) protein expression responses are dichotomously different. B. burgdorferi infection strongly and selectively upregulated CD1a, CD1b and CD1c gene products with no discernable effects on constitutively expressed CD1d. The constitutive expression of CD1d Terminal deoxynucleotidyl transferase at all stages is consistent with its proposed function in activating NKT cells during the earliest stages of innate immunity. In contrast, the group 1 CD1 isoforms are not commonly expressed on circulating monocytes or at high levels or on uninflammed dermal skin and so require some antecedent stimulus of the innate immune system before APCs become competent to activate T cells. We found evidence for group 1 CD1 upregulation as an early event in Lyme disease pathogenesis and developed a new clinical model to study of human CD1 proteins in situ. Results obtained on dermal DCs in vivo, ex vivo

(Fig. 1) or with dispersed myeloid cells in vitro generally agree with one another and show marked upregulation of group 1 CD1 proteins. However, some differences were seen based on the route of the infection, the types of cells or the particular CD1 isoform analyzed. Bright staining for group 1 CD1 proteins was seen at the margin of certain EM lesions, providing clear evidence that CD1 can be expressed at the site of the spread of spirochetes early in the disease. Many patient samples did not show CD1 expression present above baseline levels (Table 1, Fig. 1A), but CD1b and CD1c upregulation was seen in all cases when the infection was carried out under controlled experimental conditions that avoid sampling bias. In no case did we see strong expression of group 1 CD1 in the dermis of uninfected skin (Fig.

73 m2 had worse global cognitive function (5 studies, 2,549 parti

73 m2 had worse global cognitive function (5 studies, 2,549 participants, SMD −0.63, CI −1.05 to −0.21) (figure 1). Specifically, participants with GFR <60 ml/min/1.73 m2 performed more poorly in tests of attention (5 studies, 7,346 participants, SMD −1.04, CI-1.68 to −0.40), memory (4 studies, 3,392 participants, SMD −0.18, CI −0.36 to −0.01) and executive function (5 studies, 2,992 participants, SMD −1.02, CI −1.02 to −0.18). Scores for language skills (3 studies, 2,369 participants, SMD −0.24, CI −0.57 to +0.08) and processing

speed (2 studies, 4,969 participants, SMD −3.09, CI −8.76 to +2.57) were no different. Cognition worsened as GFR declined, with global cognitive function (p = 0.003) and executive function (p = 0.05) test scores poorer

when GFR <30 ml/min/1.73 m2 versus GFR 30–60 ml/min/1.73 m2. Conclusions: CKD affects global cognitive function and worsens with advancing CKD, with attention and executive function BMS-354825 research buy being particularly affected. A more detailed understanding of the cognitive effects of CKD is needed as it has implications for patient education, chronic disease management and transplant work-up. YAMAMOTO RYOHEI1, see more SHINZAWA MAKI1, ISHIGAMI TOSHIHIRO1, TERANISHI JUNYA1, KAWADA NORITAKA2, NISHIDA MAKOTO2, YAMAUCHI-TAKIHARA KEIKO2, RAKUGI HIROMI1, ISAKA YOSHITAKA1, MORIYAMA TOSHIKI2 1Department of Geriatric Medicine and Nephrology, Osaka Univeristy; 2Osaka University Health Care Center Introduction: Some studies reported that soft drink consumption predicts cardiovascular disease and its risk factors

such as diabetes, hypertension, and metabolic syndrome. On the contrary, only a little information is available about an association between soft drink consumption and incidence of chronic kidney disease. Methods: Eligible participants of this retrospective cohort study were 12026 Osaka University employees aged ≤65 yr who visited Osaka Rebamipide University Healthcare Center for their annual health examinations between April 2006 and March 2011. A total of 7976 participants (66.3%) were included who had ≥60 mL/min per 1.73 m2 of eGFR, negative or trace of dipstick urinary protein, or no current treatment for kidney diseases at their first examination. Baseline soft drink consumption at the first examination (0, 1, and ≥2 drinks/day) was obtained from the self-reported standard questionnaires. The outcome of interest is proteinuria defined as ≥1+ of dipstick urinary protein. An association between soft drink consumption and incidence of proteinuria was assessed using Log-rank test for trend and multivariate Poisson regression models adjusting for clinically relevant factors. Results: The baseline characteristics of 3579 (44.9%), 3055 (38.3%) and 1342 (16.8%) employees with 0, 1, and ≥2 drinks/day of soft drink consumption were as follows; age (yr), median 30 [interquartile range 29–42], 32 [27–39], and 34 [29–42] (Ptrend < 0.001); male gender 46.0%, 49.4%, and 62.9% (Ptrend < 0.001); body mass index (kg/m2), mean 21.